The goal of this program of projects is to use spontaneously occurring canine tumors effectively in experimental cancer therapy. Preliminary studies of various modalities of cancer therapy can be done in dogs with greater latitude than in humans. Valid bases for extrapolation to man can be provided if large animal species with similar tumor types are studied. The objective in development of new therapeutic approaches is to achieve tumor control with minimal normal tissue damage. For most of the proposed projects, statistical comparisons can be made of doses required for tumor control and normal tissue complications for different modalities. In other projects toxicity and tumor bed effect will be emphasized, although some estimate of tumor control also may be obtained. The toxicity studies are particularly relevant because they will be done in diseased and older animals. Estimates of therapeutic gain will be made over a range of doses. Late effects will be evaluated for all studies. The effective use of spontaneous canine tumors may obviate the use of humans as preliminary test systems for screening cancer agents and for toxicologic evaluations. These studies can lead more quickly to the acceptance of new modalities in human medicine. The projects are: 1. Continued development of an animal tumor research center. 2. Studies of localized hyperthermia and irradiation for oral squamous cell carcinoma and melanomas. 3. Physiologic and toxicologic studies of whole body hyperthermia in normal dogs and dogs with disseminated cancer. 4. Evaluation of a radioprotector and localized irradiation of soft tissue sarcomas. 5. Use of radioprotective agents to reduce toxicity of total body irradiation and chemotherapeutic agents. 6. Response of abdominal tumors and normal tissues of the tumor bed to intraoperative irradiation.